Launched, Active, and Recruiting!

Investigating the Genetic and Developmental Basis of Lipoedema

 

By Erik Lontok

The Lipedema Foundation is proud to announce the ethics approval and launch of a new Australia-based, multi-institutional collaboration designed to study the genetic and developmental basis of lipoedema! During my recent visit Australia, I was hosted by LF Team Adelaide grantees Chris Hahn, Eric Haan, Natasha Harvey, Kelly Betterman, and Hamish Scott (Figure 1), as well as Neil Piller, Michelle Parsons, and Marielle Esplin (not pictured, but met!). The research study was announced and recruitment began during the 2018 Lipoedema Australia National Conference.

   
  
  
  
  
   
   
    
      
     
      Figure 1: Dinner and Science with (from
    left-right) Chris Hahn, Eric Haan, Erik Lontok, Natasha Harvey, Kelly
    Betterman, and Hamish Scott.    
     
      
    
   
    
  
  Figure 1: Dinner and Science with (from left-right) Chris Hahn, Eric Haan, Erik Lontok, Natasha Harvey, Kelly Betterman, and Hamish Scott.

Figure 1: Dinner and Science with (from left-right) Chris Hahn, Eric Haan, Erik Lontok, Natasha Harvey, Kelly Betterman, and Hamish Scott.

Our discussions focused on the institutional and administrative challenges involved in launching a multi-institutional collaboration. For example, unlike single or multi-institution studies in the U.S. that require only an ethics approval from each organization’s Institutional Review Board (IRB), Australian research institutions require both ethics and governance approval, the latter involving documentation that justifies why the proposed research must occur at that particular institution.

 Figure 2: Left, PacBio Sequel Platform (left) and Roche GS Juior, hidden behind boxes (right).

Figure 2: Left, PacBio Sequel Platform (left) and Roche GS Juior, hidden behind boxes (right).

Another notable aspect of the Team Adelaide award is their process for return of results from actionable findings. Given the immense capability of genetic sequencing to identify single base pair changes in our genomes, which can be normal or involved in disease, studies of this type are ideally required to establish a process for sharing with study participants what certain actionable findings might mean for them. While we do not yet know what each of these changes mean, when researchers find a result that they can interpret and connect to a specific result, our colleagues in Australia are then well-suited to explain what these results might mean to an individual!

One of the highlights of my trip was a tour of the South Australia Centre for Cancer Biology, one of the leading accredited centers in Australia for pathological sequencing of patient samples for disease and genetic markers. Hosted by Professor and Co-Principal Investigator Hamish Scott, the tour exposed the exciting breadth of the Centre’s DNA sequencing capabilities. Their long and storied experience in this field was evident from not only their extensive single cell and transcript platforms, but also their  2nd generation PacBio Sequel System (released 2015) and their 1st generation Roche GS Junior  (released 2005), occupying the floor next to the PacBio platform (Figure 2).

The study, which is now enrolling patients, is open to anyone based in Australia. More information can be found in their research flyer here.

We are excited and eager to find out what Team Adelaide will learn about the genetic causes and drivers of lipedema, and look forward to sharing progress updates on this promising endeavor.

"A rising tide lifts all boats": Lymphatic Impact Researchers

by Erik Lontok

We’ve long believed that advancing lipedema biology would impact the scientific disciplines and fields close to lipedema – in particular, lymphatics research. So, in honor of Lymphedema Awareness Month (March), we would like to highlight a few of the LF grantees whose research efforts will not only improve the way we define and diagnose lipedema, but also advance our overall understanding of the lymphatic system.

Kim To and Brandon Dixon, Georgia Institute of Technology

  • Input: Mouse model
  • Hypothesis: Targeted nanoparticle-based delivery of calcium channel activators to lymphatics will result in enhanced lymphatic pump function and a reduction in the local adipose tissue volume, while minimizing unwanted off-target effects to the blood circulation.
  • Potential: Kim’s research has the potential to serve as a drug delivery system targeted to the lymphatic vessels. The best part is that she is designing a vehicle – with the possibility that different kinds of drugs may ride in it!

 Rene Haegerling, St George's University of London

  • Input: Tissue sample
  • Hypothesis: Light-sheet microscopy-based imaging techniques will allow visualization of the 3D microanatomy of lipedematous tissue and could therefore elucidate vascular alteration in patient tissues.
  • Potential: A more detailed knowledge about the vascular architecture will improve our understanding of the disease and could result in a diagnostic test for lipedema. Rene’s previous research has generated detailed 3D images of control, lymphedema, lymphangiomatosis tissue samples. Addition of lipedema to this panel will allow us to compare the level of vascularization across all the conditions and visualization of the impact of lymphatic diseases.

 Michelle Foster, Colorado State University

  • Input: Mouse model
  • Hypothesis: Fat dysregulation that occurs with lipedema is caused by aberrant estrogen signaling.
  • Potential: Foster’s mouse model has the potential to assess the downstream impact of estrogen dysregulation on the immune state and function of the lymphatic capillaries, vessels, and node.

Adri Chakraborty and Joe Rutkowski, Texas A&M University

  • Input: Mouse model
  • Hypothesis: Increased adipose tissue growth in a VEGF-D mouse model will result in altered lymphatic density, nerve function, and inflammatory profile that would contribute towards understanding lipedema physiology.
  • Potential: Adri’s work will expand our understanding of how lymphatics might ideally grow to support increased adipose deposition.

 Manus Donahue and Rachelle Crescenzi, Vanderbilt University

  • Input: Study participants
  • Hypothesis: Lower extremity (i) sodium and (ii) fat-to-water ratios, as measured using non-invasive MRI, are uniquely elevated in patients with lipedema relative to body-mass-index matched healthy adults and adults with lymphedema.
  • Potential: If confirmed, findings could provide information for a quantitative diagnostic test that distinguishes lipedema from other conditions with overlapping external presentation. Specifically, Manus’ direct comparison of lipedema and lymphedema may allow for a differential diagnostic between the two diseases.

We are enthusiastic about the progress being made by these investigators, and look forward to sharing research outcomes as they become available.  In the meantime, if you’d like to learn more about lymphatic impact researchers, please also see:

Thank you for taking the time to learn about our efforts to expand the lymphatic research space.  We look forward to helping raise the collective tide around lipedema and lymphatics research.

 

“You won’t know until you do the experiment”: Update on the LF 2017 Grant Cycle

by Erik Lontok

This is an inherent truth about research, and the most common response I heard from my principal investigators (PI) all through undergrad and graduate school – that even with the best of hypotheses, you can’t possibly know what the outcome will be until a study has been conducted. As we found out earlier this year, the same is true when funding research. In medical philanthropy, as in science, all you can you can do is plan ahead, think through every possibility, and prepare to be surprised. 

During our 2016 grant cycle, a common statement we heard from applicants was: “Would you provide me with more information on how the process works?” Although we did our best provide an overview of the grant submission and review process, we knew that it would be an iterative exercise, tailored to the challenges of building a brand-new field of study around a poorly defined disease.

Now that research is underway, we’ve taken a moment to step back, assess the funding process, and evaluate our learnings. Following is a brief summary of that process, including the key criteria for successful applications: 

  • 40 LOI’s reviewed – Submitted letters of intent (LOI) were reviewed based on the strength of the hypothesis along with specific aims, research methods, and relevance of the proposed work to lipedema. Scientific merit was assessed through the relevance and feasibility of the work, as well as the applicant’s research tools, experience, and collaborative history.
  • 28 researchers interviewed – Meritorious applicants were interviewed via videoconference and Powerpoint, wherein their proposal, research experience, interest in lipedema, relevant tools for the field, and collaborative potential were discussed. A key interview topic involved modification of the scope of the submitted LOI, either through learning about the types of collaborations that would enhance their work, or encouraging a focus on utilizing patient samples as the project’s model system.
  • 22 applications invited – Submitted full applications included a greater expansion of specific aims, proposed alternate research approaches, defined project milestones, and a detailed budget. Application criteria included:
    • Will this work define lipedema pathophysiology or advance our understanding of disease etiology?
    • Might the work lead to the development of a diagnostic tool?
    • Are the proposed methodology, study design and controls, clear and relevant to the project’s hypothesis?
    • Does the project establish the dataset needed for externally funded applications?
  • 16 projects awarded - The final decision point was assessment of the collaborative potential of the researcher and their proposed work. This was the most subjective component of our review process, but has now led to:
    • A collaboration is under development with all three of our genetics-focused projects.
    • Two co-located teams of surgeons and researchers.
    • Initiation of a sample-sharing agreement with a clinical project and a diagnostic tool researcher.
    • Eight additional collaborations.

Apart from refining the process itself, we also learned and collected data points about applicant scoring, such as:

  • Applicants that could not succinctly state their hypothesis, or that struggled to articulate the relevance of their work to the challenges facing lipedema typically rated poorly.
  • A feasible project plan with lofty, but achievable research goals scored well.
  • Beyond scientific merit, the best applications involved researchers proposing and willing to participate in collaborations.

Allow me to end this blog with my PI’s most common response after showing them research data, “well that answers that – and now here are all the questions the answer raises. Get to it.”

And as we move into 2018, these are the questions we will be asking ourselves about our research program:

  • How might we best foster productive collaborations?
  • How do we balance the scientific freedom researchers need to succeed, with the goals and milestones put forth in applications?
  • How can the foundation facilitate discussions about unpublished, preliminary work whilst protecting a grantee’s research and intellectual property?
  • How might our current grantees and work engage equally talented and driven researchers into thinking about lipedema?

We will be sure to keep you posted as more data is generated. In the meantime, don’t hesitate to reach out with any questions, and thank you for your continued interest and support.

2017 Lipedema Foundation Funding Cycle and Grantees

By Erik Lontok

Earlier this year, informed by the unmet needs and key research efforts identified by our 2016 Lipedema Scientific Retreat, the Foundation issued a formal request for grant applications aimed at advancing lipedema research and exploring the genetic basis of the disease. We’ve recently concluded our 2017 funding cycle, and are pleased to announce our awarded proposals here.

Given that this was the Foundation’s first formal grant cycle, we were impressed by the volume and caliber of submissions received.  A total of 37 research applicants, representing a broad range of scientific disciplines and institutions worldwide, submitted Letters of Intent (LOI). After carefully reviewing each LOI and conducting follow-up interviews, we extended 20 invitations to submit a Full Application, of which 13 were ultimately awarded milestone-driven research grants ranging from 1-3 years.

A clear trend amongst the awarded projects was the active engagement of individuals with lipedema, whether through the development of diagnostic and imaging tools or the utilization of patient samples. Our hope is that by fostering more patient-centered research, we can accelerate the pace of discovery and improve diagnosis and treatment options for lipedema patients.

Overall, we are heartened by the number and quality of the submitted LOIs and full applications, as it reflects our community’s growing demand for better treatments and indicates increasing scientific interest in lipedema. We are excited to partner and support the research of our 2017 grantees, and to continue our engagement with the patient community, as we believe it will take a village to successfully understand and address lipedema.
 

PHILANTHROPIST’S FOREWORD

By Felicitie Daftuar

(The following was also used as the forward in the Milken Institute's Giving Smarter Guide for Lipedema.)

I was told to stop having children by the first therapist who confirmed my suspicion of lipedema. I was told to go to Germany, get liposuction and wait 18 months before continuing to have children by an expert. I was told by my amazing GP that the lump of fat and fluid under my knee was postpartum depression, even though I wasn't depressed.
 
I hired a concierge medicine company to investigate 1) Is lipedema a real thing? 2) Do I have it? 3) What should I do about it? Months later: Yes, Yes, We don't know.
 
So I did what others before me did. I searched Pubmed and Google Scholar for research papers. I read some of them. I put them in a spreadsheet.
 
I joined Facebook groups and LinkedIn-ed people I thought would help. I went to patient, researcher, and therapist conferences. I helped resurrect a defunct non-profit, the Fat Disorders Research Society, and the team set up a website and hosted 2 patient conferences (one with 270 attendees!).
 
In 2015, I narrowed my focus to research, started the Lipedema Foundation (LF), and started funding research projects.
 
But I kept coming up short. How could a disease that's seemingly everywhere have so little published? Sure there are some descriptive papers, case reports, and studies with a few patients. There are even literature reviews. But no pathogenesis. No genes. No blood test. No biomarkers. No replicable imaging test. Nada zip zero. I couldn’t find answers to my questions about lipedema.
 
Why are pain and swelling (which are subjective) recognized criteria of lipedema, but the physical change in the texture of the fat is not?
 
Why are there only 5 US physicians willing to diagnose lipedema, but there are 12 surgeons willing to operate, 100s of therapists willing to treat, and 2,000 patients participating in Facebook groups?
 
Do my relatives have it? Are my 3 daughters going to get it? How could it be that I carried 3 children, and my abdomen looks better, but my legs look worse? Is it a disease? A condition? A syndrome? I don't feel sick, but my body is different.
 
Why can I feel nodules of fat in my legs, but no one can image them with ultrasound, MRI or a highly technical piece of equipment?
 
Why is it that if I cook healthy meals and exercise the right way, I don't have pain, but if I go on vacation my legs burn when I lay down at night? Do I really need liposuction if my BMI is in the 20s?
 
Will it get worse? Will it get better? Will it ever go away? How is lipedema different from lymphedema, obesity, lipodystrophy and Dercum’s Disease? Is the prevalence really 11% of post-adolescent women? Or 5%? Or 1%? How was I now one of the world's experts in a medical condition?
 
Along came a small band of heroes. People who had seen this before. People who thought I wasn't crazy for hunting for answers. People who raised the level of discourse around something that had been predominantly patient-led discussions. People who know the ins and outs of the typical disease path from diagnosis to treatment to cure.
 
The Milken Institute’s Center for Strategic Philanthropy (CSP) opened doors I couldn't. They persevered through setbacks that were tough for me to deal with. They remained objective and focused, diving down deep into many facets of the biology and then resurfacing to put the big picture together.
 
CSP could talk to researchers and doctors on their level. They could assess which expertise of researchers were needed in order to move forward, and brought 20 different specialties into the conversation. The heroes are so well networked around DC that they could get both the NIDDK and NHLBI represented at our first ever Lipedema Scientific Retreat. They invited me to sit at tables with other people like me.
 
They kept my expectations grounded and at one point told me: we are at the very beginning of the course of this disease; we know nothing. But they provided a roadmap and tools to move forward, via both this Giving Smarter Guide and an invaluable private report identifying names, tools, and projects. I became we. We went to conferences and called people around the world. We worked together. We wondered together. We opined together. We hosted a meeting convening a global cohort of the best-of-the-best and, and together at the Scientific Retreat, we mapped out the gaps in the field of lipedema research so that we could collaborate and coordinate the research needed to define the space.
 
We have chosen to strategically address key research challenges of lipedema. For the short term, LF's first priority is the science behind the cause(s) of lipedema. We cannot do meaningful research into lipedema treatments until we understand the scientific cause(s) of the condition. There is a lack of scientific consensus on the most basic elements of this disease, and LF has set about to fix that. We can’t get anywhere until we tackle the fundamentals.
 
Please, read on and become part of our journey. Take notes and jot down ideas, then call LF. We'll be happy to talk to you about your ideas to move this forward. We have a long road ahead of us and we'd like your company, because it takes a village to move diseases forward. Felicitie Daftuar Founder and Executive Director Lipedema Foundation