LAM Treatment Alliance Fast Tracking Treatment Research

Summit Objectives: Milestones related to committee projects advanced in Toronto, Berlin and Milan will be re-visited and further advanced at this face-to-face Committee meeting.

Power Point presentation from summit

Summit Objectives: Despite being at the heart of the morbidity, mortality and pathophysiology in lymphangioleiomyomatosis (LAM), surprisingly little has been understood about the particular nature and mechanism of lung destruction. This Summit was dedicated to identifying key questions, information exchange among leaders in relevant diseases and mapping critical next step projects to advance knowledge required for clinically relevant interventions for women with LAM. What do insights into lung destruction, modeling, repair and regeneration teach us about how to effectively treat and eradicate LAM?

Summit Key Question: "If money were no object but time was in short supply, what would be critical to learn about lung destruction, modeling, repair and regeneration in LAM in order to advance the most high impact clinically relevant interventions for women living with the Disease?"

Participant Bios, Photos and Background Readings
Summit Agenda
Summit videos

Objective: Milestones related to committee projects launched in Toronto and Berlin were re-visited and further advanced at this face-to-face Committee meeting. The International LAM Registry pilot was presented for feedback and the first project for the Registry was identified.

3rd International Congress on Pulmonary Rare Diseases and Orphan Drugs
Power Point presentation from summit

Objective: Systematically explored the leading-edge imaging modalities that could be relevant to overcoming key barriers facing LAM treatment research. Progress was made through bi-directional, multi-disciplinary knowledge-sharing and discussions of concrete next steps that can be fast-tracked through collaborative LAM / radiology community efforts.

Summit Agenda
Summit Participants
Attendee List
LAM Background Readings
Imaging Background Readings
Summit Video

In April 2008, the LTA convened a group of senior LAM researchers and clinicians with the Director of the National Chemical Genomics Center at the National Institutes of Health to discuss doing the first drug screen in LAM. The goal was to take advantage of one of a remarkable effort first led by Francis Collins of the human genome project, and then by Chris Austin, to bring greater high throughput screening technologies traditionally relegated to the private sector into the public sector in service of rare and neglected disease. Our project objective was to learn which approved drugs, ideally alone or in combination, might kill what we understand to be LAM cells, and in doing so give us new and important clues into the biology of the disease and help us prioritize drugs for small clinical trials. Thanks to tremendous commitment and generosity of time and expertise of our advisory team and Dr. Austin’s NIH-based biotech or dream team of biologists, chemists, informaticians and engineers, the first approved drug library screen was completed in June of 2008 using surrogate LAM cell lines. In record time, results were validated, analyzed and further validated. Additional screening was done and preliminary results were discussed during various conference calls. On December 11, 2008, Chris Austin and the LTA brought experts from across fields relevant to LAM together with the experts in the chemical screening process to make sense of the LAM screen results and to chart an aggressive way forward. That was the focus of this important session. More details about follow-up projects now in formation are coming soon.

Chris Austin also gave the seminar talk on December 11th and although he described the LAM drug screen in that talk, he did not publicly release the results of the screen. Watch the December 11, 2008 Seminar video to learn more about the LAM approved drug screen or about NIH-NCGC’s history and approach to accelerating the pace of treatment research for rare and neglected diseases.

Special thanks to the LAM project advisory committee on the collaboration with Chris Austin, MD and team: Lisa Henske, MD, Joel Moss, MD, PhD, Vicky Whittemore, PhD, Cheryl Walker, PhD.

Summit Agenda
Summit Participants

Objective: The role of this committee with regard to global coordination of clinical trials in LAM was stressed and strategies for coordination were discussed with a focus on advancing concrete efforts. Projects related to retrospective and prospective tracking off-label use of drugs by LAM patients globally were addressed.

This Brighton Summit focused on further accelerating the growth, development and effectiveness of the LAM/TSC community coordination worldwide. In Brighton, the LAM Treatment Alliance worked closely with our Tuberous Sclerosis Alliance and Tuberous Sclerosis International partners to strategically address new forms of global patient-researcher collaboration and coordination of clinical trials. Through focused workshops, patients, patient family members, researchers and clinicians will shape new initiatives along with the direction of tissue and data-sharing efforts already underway, specifically as they relate to those launched at the LAM Global Patient Summit held in Oxford, UK this past January. These initiatives include the internationalization of LAM tissue donation, procurement and distribution program and LAMsight, an internet-based data-sharing platform enabling patients and researchers to collaborate in search of a cure far more quickly than has heretofore been possible. These meetings will be streamed live via the Internet for remote global participation to ensure that our feedback process and global initiatives are maximally inclusive across countries, institutions and LAM/TSC organizations.

• Participant Bios
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At the LAM Disease Model Summit, we focused on overcoming the challenges of modeling LAM. Without a useful model for the disease, we struggle to scale-up efforts to explore therapeutic options in an effective and efficient way. At this meeting, we brought together LAM experts with leaders in relevant fields and presented those from outside the field with a comprehensive look at some of the approaches to modeling the disease that have been / are being attempted. We mapped out next steps toward overcoming hurdles we face and discussed how the LAM Treatment Alliance can concretely support these initiatives.

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• Participant Bios and Relevant Work

The LAM Treatment Alliance is dedicated to fostering and funding research that can lead to an effective treatment for LAM in the fastest time possible. The LAM Cell Summit held in June of 2006 sought to review and establish criteria for validating LAM cells. As we now consider the outstanding bottlenecks we face in scaling-up and advancing treatment research, our focus at the LAM Cell Summit 2008 was on both strategic and tactical/technical challenges.

At the LAM Cell Summit 2008, we revisited the reasons why identifying, describing, validating, purifying and growing these cells matters. We thought across disciplinary boundaries and drew on respective labs' experiences working with these cells and those with similar characteristics. We came up with new insights, alternatives and potential best practices to guide us as we embark on concrete initiatives that emerged as top priorities. Our outcome report will follow. Stay tuned!

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• (Outcome Document Pending)

The LAM/TSC Hormone Summit brought together experts in LAM and TSC with leaders in fields relevant to understanding the influence of hormones in both diseases. The smooth muscle-like cells that invade the lung to cause LAM are also present in the renal angiomyolipomas in both TSC and LAM and seen in lymph nodes and other organs in individuals with both diseases. Given the distinct sex bias in LAM (only a few cases reports of LAM in men with TSC whereas ~40% of women with TSC develop LAM, and sporadic LAM only occurs in women), we discussed the cell of origin, the theory of the disease, models for the disease and the influence of hormones on the function of these cells and in these models. Concrete research initiatives needed to advance this important area of investigation were mapped as next steps.

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• Gender and Hormonal Influence Background Doc
• (Summit outcome report to follow)

• Participants
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• Global LAM Patient Summit 2008 Summary Report and Next Steps
• Summit Report Chinese
• Summit Report French
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The LTA has been working to build networks that support research globally so that every country and every LAM organization can be maximally involved in the search for treatment. This meeting focused on concrete steps to ensure that patient coordination is useful to making research progress in the fastest time possible. Patient representatives from LAM organizations from 17 countries where LAM patients are known attended, as well as researchers and drug company partners. Sessions addressed ways that patients can support treatment research through tissue procurement efforts and via global patient-researcher database developed by LTA-MIT Media Lab partnership where patient participation is crucial. We also provided updates on clinical trials underway or in the pipeline and discussed ways for LAM patients to coordinate with researchers and drug companies seeking candidates for a drug trials.

Global LAM Patient Summit 2008 Critical Outcomes
The LTA Global LAM Patient Summit achieved international agreement to start work immediately with NDRI to coordinate a worldwide LAM tissue donation and researcher access and distribution program. Representatives also agreed to pursue the LAMSight project, a collaboration between the LAM Treatment Alliance, MIT Media Lab, Dana-Farber Cancer Institute and other partners, which uses cutting-edge media technologies to create a global research network of patients with the disease and researchers working to effectively treat it; a critical step towards research progress. LAMsight will be in beta-testing for the next few months.

This focused problem-solving forum brought key LAM researchers together with world leaders in fields relevant to overcoming critical barriers to finding an effective treatment for LAM. Critical developments emerging from the meeting included the identification of new approaches to overcoming challenges related to tissue access; modeling the disease, culturing LAM cells and targeting therapy. LAM cell clusters were highlighted as a potentially productive source of LAM cells and a rich medium in which they can potentially be cultured. Topics included: fostering and coordinating strategic collaborations to address gaps and barriers; LAM tissue availability; isolating and defining LAM cells; best practice guidelines for clinical management; improving hypothesis generating tools available to researchers, and more. The LAM Treatment Alliance is tremendously grateful for the tremendous generosity our Scientific Advisory Board as well as the Karolinska Institute co-hosts and for the time, interest and commitment of our individual researcher/clinician delegates.

• Participant Bios, Photos and Relevant Work

Established validation criteria for LAM cells and planned next steps for greater tissue access by more scientists.

• Summit Agenda / Participant Bios

Established priority research streams for accelerated treatment research.

• Summit Participant Bios