How We’re Organized
Target ALS has driven the emergence of new therapeutic programs in several ways, by:
(a) Coordinating and funding high-level academic consortia for the discovery and validation of new candidate therapeutic targets;
(b) Supporting target-focused collaborations between academia and pharma/biotech, including in some cases direct funding of the for-profit partner;
(c) Attracting new investigators with relevant expertise to the ALS field;
(d) Establishing specialized core facilities to provide the international ALS community with access to resources such as post-mortem tissue, target validation in vivo and human stem cell-based technology;
(e) Facilitating the transition of talented young investigators to an independent career in ALS research. These Springboard Fellowships provide a valuable kick-start during the difficult career transition from the status of postdoctoral fellow in an established laboratory to that of new assistant professor with everything to prove.
To streamline its involvement as a catalyst, Target ALS does not seek intellectual property or other forms of ownership. To ensure that the funds are administered in a time-effective and transparent manner, we have established a structure that clearly identifies roles in defining and approving overall strategy (Board and Independent Review Committee), evaluation of funding requests (Independent Review Committee), addressing conflict of interest issues (Conflict of Interest committee) and execution (Central Administration), as illustrated here:
The current members of the different components of the Target ALS administration structure are as follows:
Target ALS Administration
Chris Henderson, Ph.D. (Chief advisor; Biogen)
Leonard Petrucelli, Ph.D. (Chief scientific advisor; Mayo Clinic)
Manish Raisinghani, MBBS, Ph.D. (President)
Kenneth Devaney (Treasurer)
Jesse Bailey (Executive director of institutional development)
Daniel L. Doctoroff (Chair)
Zach Hall, Ph.D.
Story Landis, Ph.D.
Don Cleveland, Ph.D. (Ludwig Institute for Cancer Research)
Kevin Eggan, Ph.D. (Harvard University)
David Holtzman, MD (Washington University)
Jeff Rothstein, M.D., Ph.D. (Johns Hopkins University)
Mike Poole, M.D. (Bill & Melinda Gates Foundation)
Stacie Weninger (F-Prime Biomedical Research Initiative)
Independent Review Committee (IRC)
Robert Miller, Ph.D. (Chair, George Washington University)
Michael Ahlijanian, Ph.D. (Bristol- Myers Squibb)
Manzoor Bhat, M.S., Ph.D. (University of Texas Health Science Center, San Antonio)
Moses Chao, Ph.D. (New York University)
Kurt Fischbeck, M.D. (National Institutes of Health)
Jonathan Glass, M.D. (Emory University)
Zaven Kaprielian, Ph.D. (Amgen)
Robert Mays, Ph.D. (Athersys)
Mahendra Rao, M.D., Ph.D.
Rajiv Ratan, M.D., Ph.D. (Cornell University)
Ian Reynolds (Teva)
Wim Robberecht, M.D., Ph.D. (University of Leuven)
Ajay Verma, M.D., Ph.D. (Biogen)
Andrew Wood, Ph.D. (CHDI)
Frank Walsh, Ph.D. (Ossianix)
Richard Olson, Ph.D. (Bristol-Myers Squibb)
Craig Wegner, Ph.D. (AstraZeneca)
Eric Schaeffer (Johnson & Johnson)
Conflict of Interest (COI) Committee
Zach Hall, Ph.D. (Chair)
Daniel L. Doctoroff
Robert Miller, Ph.D. (George Washington University)
James Treanor, Ph.D. (ADRx)
Neil Shneider, M.D., Ph.D. (Columbia University)
Management of Target ALS Research Programs
Target ALS is proud of its decision to fund only pre-structured collaborative projects but recognized from the start that it is necessary to ensure that each consortium reaches its full potential and shares data with the Target ALS community and beyond in real time. To do this, we have instigated several mechanisms:
a) Regular face-to-face consortium meetings between participants, including principal investigators and fellows. These have proven irreplaceable in allowing for direct discussion of results and potential controversies to present to the wider Target ALS community
b) “Post-doc meetings” in which only the junior members of a given consortium exchange experiences and data of common interest
c) Bi-annual reports on scientific progress, which are reviewed by the Board and IRC
d) Certified annual financial reports on uses made of Target ALS funds
Last but not least, the Target ALS Annual Meeting (held at Columbia University, see illustrations throughout the website) brings together not only all funded investigators and fellows but also representatives of biotech/pharma companies interested in becoming involved in ALS. At this meeting, multiple approaches are taken to ensure mixing of scientists of different backgrounds, creating a unique osmosis between academic researchers and their industry counterparts. As an example, at the June 2015 meeting there were 194 participants from 26 academic/non-profit institutions and 19 different pharma/biotech companies.
Human Postmortem Tissue Core
Despite the critical need to validate hypothesis on human material, there has been no publicly available searchable tissue bank focused on specific CNS regions, muscle and nerve from ALS patients and controls.
Target ALS has created the first multicenter postmortem tissue core dedicated to ALS research. For the first time a multicenter policy at harmonization of SOPs for donor recruitment, tissue acquisition, processing, storage, histopathological characterization, and archiving have been implemented to build up a bank of high quality ALS postmortem tissue.
A web-based searchable database (explore Target ALS human postmortem tissue inventory) gives investigators the number of Target ALS human postmortem cases that meet basic demographic criteria as well as fixed and frozen tissue that is available. Additional case characteristics and tissue regions can also be requested. Many of our Core Sites have pre-existing tissue collections in addition to the Target ALS cases, which they are happy to share through collaboration according to host institution practices. The pre-existing case collections are not included in this search.
A new open-access, high-quality whole genome sequenced dataset of post-mortem tissue samples from Target ALS is freely available to investigators in the New York Genome Center’s recently launched MetroNome clinical genomics database. For more details and to access MetroNome, go to: https://metronome.nygenome.org/TargetALS/
The samples are being RNA sequenced and are clinically annotated, with zero embargo on use. To access the RNAseq data, please contact firstname.lastname@example.org
The dataset currently includes 132 samples and will be continuously updated in real time going forward. The dataset also includes some contributions from other entities that met Target ALS’s criteria for high quality and zero embargo on use.
How to use the search:
Subject Characteristics - If more than one box is checked for a given criteria, cases with either criteria will be included. For example, if both “SOD1” and “C9orf72” are checked, cases with either mutation will be included in the results.
Tissue Regions - The search will return only cases that include all of the selected regions. For example, if “fresh frozen tissue,” “muscle,” and “primary motor” cortex are selected, the results will include cases for which both frozen muscle AND motor cortex are available.
Investigators can send requests for tissue using the Tissue Request Form and information to the postmortem tissue core director Dr. Lyle Ostrow.
Target Validation Core
At present, the single most important argument for the therapeutic potential of a candidate target is to show that when the target is modulated in mutant SOD1 ALS model mice, it confers significant benefit in terms of muscle strength and lifespan. Yet only a small number of targets have been evaluated in this manner due to the associated cost and duration of the experiments, intrinsic variability of experiments when not subjected to appropriate quality control and the fact that the techniques involved are not familiar to all investigators.
Building on the expertise of multiple Target ALS laboratories, Target ALS has created an infrastructure based on contract research organizations that is capable of evaluating targets using a panel of early outcome measures with high predictive value, which will also reduce time, cost and variability.
Investigators will need only to submit proposed targets for evaluation with a detailed justification. Once the Independent Review Committee prioritizes each project, the facility will be able to perform the central experiments and return the data to the investigator.
Please send your proposal to Manish Raisinghani (email@example.com). The guidelines for proposal format are in the documents below.
Human Stem Cell Core
The potential of human stem cell models for casting light on ALS disease mechanisms, and for testing drug candidates, is clear but largely unexplored. Establishing this technology is a major undertaking for any individual lab so Target ALS has worked to make it accessible to the ALS researchers in academia and pharma/biotech industry worldwide. The cell lines are provided with no reach-through on data or intellectual property.
Target ALS has created a network of contract research organizations and academic core facilities to generate and distribute new iPS lines, reporter lines, isogenic controls and is working to make available neural stem cells.
Current repository (order stem cell lines from repository — instructions on how to order Target ALS stem cell lines).
|Rutgers ID||Target ALS ID||Description||Gender||Race/ Ethnicity||ALS or Control||Age at Biopsy||Age at Onset||Age at Diagnosis||Age at Death||Diagnosis||Site of Onset||Family History|
|ALS||64||60||60||65||Definite ALS||RUE||paternal aunts w/ ALS; father w/ dementia|
|ALS||64||60||60||65||Definite ALS||RUE||paternal aunts w/ ALS; father w/ dementia|
|Control; sibling of TALS9||62||paternal aunts w/ ALS; father w/ dementia; sister w/ ALS|
|FA0000018||TALS9-11.2||C9orf72 ALS||F||Caucasian||ALS||61||60||61||Probable ALS||Bulbar||None|
|FA0000012||TALSSPO16.2||Sporadic ALS||M||Caucasian||ALS||49||47||48||53||Probable ALS||RUE||None|
|FA0000013||TALSSPO21.21||Sporadic ALS||M||Caucasian||ALS||38||35||36||45||Probable ALS||RUE||None|
|Rutgers ID||Target ALS ID||Description||Gender||Race/ Ethnicity||ALS or Control||Age at Biopsy||Age at Onset||Age at Diagnosis||Age at Death||Diagnosis||Site of Onset||Family History||Availability|
|FA0000019||TALS9-12.3||C9orf72 ALS||M||Caucasian||FTD, ALS||60||40 |
|60||Probable ALS||LUE||ALS + FTD (mother; confirmed by autopsy)||4-Mar-16|
|Control; brother of C9009||62||paternal aunts w/ ALS; father w/ dementia; sister w/ ALS||4-Mar-16|
|FA0000014||TALSTDP-47.10||TDP43ALS||M||Caucasian||ALS||43||43||43||44||Definite ALS||BLE, BUE||ALS (Parent)||4-Mar-16|
Distribution: RUCDR Infinite Biologics
Target ALS has contracted with RUCDR, a Rutgers University-based core facility for distribution of iPSC lines. RUCDR maintains, expands, performs quality control and distributes iPSC lines.
Target ALS has negotiated the price to be $500/ampule for academic/non-profit laboratories and $1,500/ampule for for-profit organizations. Each ampule will contain 2 million cells.
Please email Michael Sheldon (firstname.lastname@example.org), director of our distribution facility if you have any issues ordering stem cell lines.
We will continue to add new lines to the repository. Target ALS has also arranged that new subclones made by ALS investigators can be deposited (should the investigators so choose) and distributed through the same repository under the same MTA we have developed.
Before the end of 2016 the core plans to add the following resources (timeline TBD based on ongoing negotiations with vendors and institutions):
- Neural stem cells
- Motor neurons with Hb9 and Olig2 reporters
- Astrocytes with GFAP reporter
- Generic neurons with a DCX or MAP-2 promoter
- Media for motor neuron culture and astrocyte culture
- Reporter constructs for assessing motor neurons, astrocytes and oligodendrocytes
Confidentiality and intellectual property rights of the investigator
The data and intellectual property generated from use of these stem cell lines will reside entirely with the investigator. The material transfer agreement (MTA) associated with these cell lines will ensure there is no reach-through on the data or intellectual property generated by use of the cell lines. The MTA will also ensure that the investigator retains rights to any modifications made to the lines (e.g. gene editing and insertion of reporters) subject to any third party licensing obligations.
The consent associated with the fibroblasts used to generate the iPSC lines allows for the iPSC lines along with the relevant, de-identified clinical and demographic information to be deposited at a facility for expansion and distributed to researchers in non-profit and for-profit organizations for non-therapeutic purposes. Users will be allowed to make modifications to the iPSC lines to insert or correct mutations, insert reporters and derive motor neurons, glial cells or other derivatives from the three germ layers for non-therapeutic purposes. The de-identified iPSC lines can also be used for sequencing studies (like whole genome and RNA sequencing).
We will continue to update you progressively as more resources become available. You can reach out to Manish Raisinghani, President, Target ALS Foundation (email@example.com) with questions.
Viral Vector Core
AAV vectors have considerable potential for modulation of gene expression in the CNS in vivo, and therefore as tools for target validation. Production of high quality AAV is a costly and time-consuming effort.
To enable Target ALS investigators access to high quality AAV, we are working with Virovek , a contract research organization specializing in recombinant AAV production. Virovek is offering comprehensive gene construct design, synthesis, and cloning of transgene plasmids.
For Target ALS-funded investigators