All proceeds from Hunting and Fishing for a Cure are directed specifically to 501(c)(3) organizations which are dedicated to finding a cure for ALS. Proceeds from our charity will not go toward corporate or administrative overhead, G&A costs, etc. Our 2014 -2016 recipients were the Houston Methodist Neurological Institute, and the ALS Therapy Development Institute (ALS – TDI). The letters below provide more specifics as to how the 2014 proceeds were directed. Our 2017 proceeds will also provide funding for treating and improving the quality of life of those suffering from ALS.
Dear Amy and Rusty:
I've just returned from our national neurology meetings, and wanted to answer your queries about how we have deployed the funds from your Hunting and Fishing to find a cure fund raiser.
I join Steve in thanking you for making a difference in our collective war against the devastations of ALS.
Our annual laboratory research budget is between $700,000-$800,000. For 2014 our actual budget was $770,000. The proceeds from the 1st Hunting and Fishing for a cure were used to support our laboratory for "pre-clinical studies" to define 1. ALS monocytes and 2. ALS Tregulatory lymphocytes as potential cell-based therapies to slow the rate of ALS disease progression.
With respect to #1, we have documented that circulating monocytes from mSOD1 transgenic ALS mice and from ALS patients are pro-inflammatory and can destroy motor neurons in tissue culture. We have also documented that pro-inflammatory monocytes can be converted to protective monocytes in tissue culture. We have initiated experiments injecting the protective monocytes into transgenic ALS mice to determine whether these cell transplants can slow disease progression and prolong survival in mice. If successful, these preclinical experiments could serve as the basis for converting ALS pro-inflammatory monocytes into protective monocytes, and then transplanting the protective monocytes into the same patient from whom they were derived. A potential limitation is that human monocytes do not expand readily, and we would plan to use stem cells (derived from skin fibroblasts) that have been expanded and converted to protective monocytes. Our ability to convert stem cells from fibroblasts to monocytes has already been documented in collaboration with Dr. Clive Svendsen- Cedars Sinai Medical Center, Los Angelos.
With respect to #2 we have already documented that ALS transgenic mice and ALS patients have decreased numbers of protective Treg lymphocytes. Furthermore, transplanting Treg cells into ALS transgenic mice slows disease progression and prolongs survival. Under normal circumstances Treg lymphocytes can suppress cytotoxic T lymphocytes or pro-inflammatory monocytes. However, our recent studies have documented that human ALS Tregs are dysfunctional, i. e. they do not suppress other toxic cells.
With support from ALSFindingaCure (GE/Conair/ALSA), we have contracted with MD Anderson to expand ALS Treg cells. At present our collaborators at MD Anderson have finished the required preliminary studies, and are carrying out the necessary GMP studies and writing the protocol to obtain FDA approval.
We have been frustrated that getting to this point has been so slow, but we're very excited that the expanded Tregs which were dysfunctional prior to expansion become normally functional following expansion. This means that there are likely circulating factors in ALS patients that convert normal Tregs into dysfunctional Tregs.
Although the ALSFindingaCure sponsor is supporting the actual expansion and transplantation of Tregs, we have relied on your generosity to fund our basic science and preclinical studies including the demonstration that ALS Tregs are dyfunctional, and for helping to define the circulating factors that impair the function of the Tregs, and that promote inflammatory monocytes.
We would be honored to be chosen as beneficiaries of the 2015 Hunting and Fishing fund raiser. This support would help us retain our technical staff as well as recruit several post-doctoral fellows to help develop monocytes as potential cell-based therapy. Most critical would be studies to determine the factors causing Treg dysfunction. Discovering the cause of such dysfunction would permit us to develop therapies that could increase protective Tregs in the patient, and eliminate the need for removing the Treg, expanding them outside the body, and then transplanting them back to the patient with FDA approval.
We are extremely grateful to you, Amy, and your friends and colleagues for support of our collective efforts on behalf of all patients with ALS. Your courage, your commitment, and your passion really make a difference, and we honestly couldn't do it without your help.
Many thanks and warmest regards,
Stanley H. Appel MD
Edwards Distinguished Endowed Chair for ALS Director, Methodist Neurological Institute Chair, Dept of Neurology
We can't thank you, Amy, your family, and the Board for planning another event this year.
I agree with Stan on his points. We may not have an effective treatment today but without the annual support of families, foundations, and supports the progress would be significantly impacted.
ALS TDI has focused its investment in 2014 in the following areas:
1. Precision Medicine Program
- Invested: $2M
- The goal of the program is to collect patient medical information and medical history, track disease progression rates with accelerometer devices in real time by the second, compare the acceromoter data to self reported ALS FRS questionnaire data, sequence each patients full genome, measure protein and RNA markers in each patients blood, collect a skin biopsy and make and generate a stem cell for drug screening in the lab. Most importantly build a web portal for each patient and share all the data with each patient.
- The program has been a huge success
- 5 full time scientists
- Enrolled over 300 patients and collected samples from the first 110 already. Sequenced the first 50 genomes
- Collected accelerometer data for 6 months on more than 100 patients already.
2. Antibody targeting misfolded SOD1
- Invested $1.5M
- Collaboration with Neurimmune who owns the antibody
- Misfolded SOD1 has been found in familial and sporadic ALS tissues including blood and spinal cord
- Their antibody targeting misfolded SOD1 worked at ALS TDI in our animal model. This is the first time ever we brought in a potential treatment from an outside party and it worked in our hands to slow down disease progression in our animal model
- The are a small company and need funds to get enough antibody made to put into patients.
3. CD40L program
- ALS TDI has its own antibody targeting CD40L a protein that we have shown is instrumental in tweaking the immune system in ALS to be more neuroprotective
- We made a human antibody that we can test in people
- We are testing it in blood samples from ALS patients at Childrens Hospital in Boston to make sure its safe and to make sure it binds CD40L
- We needed funds t make enough antibody for these studies and testing in patients
- Invested $1.5M
4. Additional preclinical programs
- We have 15 other preclinical programs at various stages in the lab
Rusty and Amy I hope this helps and we know it's never fast enough but we are making progress and we couldn't do it without your help.
Chief Executive Officer & Chief Scientific Officer ALS Therapy Development Institute