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)
Manish Raisinghani, MBBS, Ph.D. (President)
Kenneth Devaney (Treasurer)

Board

Daniel L. Doctoroff (Chair)
Zach Hall, Ph.D.
Story Landis, Ph.D.
Dwight Bergles, Ph.D. (Johns Hopkins University)
Robert Brown, M.D., D.Phil. (University of Massachusetts)
Don Cleveland, Ph.D. (Ludwig Institute for Cancer Research)
Kevin Eggan, Ph.D. (Harvard University)
Jeff Rothstein, M.D., Ph.D. (Johns Hopkins University)

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)
Jesse Cedarbaum, M.D. (Biogen)
Moses Chao, Ph.D. (New York University)
Merit E. Cudkowicz, M.D. (Massachusetts General Hospital)
John Dunlop, Ph.D. (AstraZeneca)
Kurt Fischbeck, M.D. (National Institutes of Health)
Jonathan Glass, M.D. (Emory University)
Zaven Kaprielian, Ph.D. (Amgen)
Robert Mays, Ph.D. (Athersys)
Thomas Moeller, Ph.D. (University of Washington)
Mahendra Rao, M.D., Ph.D.
Rajiv Ratan, M.D., Ph.D. (Cornell University)
Wim Robberecht, M.D., Ph.D. (University of Leuven)
Georg Terstappen., Ph.D. (AbbVie)
Ajay Verma, M.D., Ph.D. (Biogen)
Andrew Wood, Ph.D. (CHDI)
Frank Walsh, Ph.D. (Ossianix)

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)

Target ALS Conflict of Policy

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.

Core facilities

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.

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 (manish.raisinghani@targetals.org). 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

Current repository (order stem cell lines from repository instructions on how to order Target ALS stem cell lines).

Rutgers IDTarget ALS IDDescriptionGenderRace/ EthnicityALS or ControlAge at BiopsyAge at OnsetAge at DiagnosisAge at DeathDiagnosisSite of OnsetFamily History
150000002TALS9-9.3C9orf72 ALSFCaucasian/
Ashkenazi
ALS64606065Definite ALSRUEpaternal aunts w/ ALS; father w/ dementia
150000003TALS9-9.5C9orf72 ALSFCaucasian/
Ashkenazi
ALS64606065Definite ALSRUEpaternal aunts w/ ALS; father w/ dementia
150000004TALS9-8.1C9orf72 ALSMCaucasian/
Ashkenazi
Control; sibling of TALS962paternal aunts w/ ALS; father w/ dementia; sister w/ ALS
FA0000018 TALS9-11.2C9orf72 ALSFCaucasianALS616061 Probable ALSBulbarNone
FA0000012 TALSSPO16.2Sporadic ALSMCaucasianALS49474853Probable ALSRUENone
FA0000013 TALSSPO21.21Sporadic ALSMCaucasianALS38353645Probable ALSRUENone
FA0000010TALSCTRL11.5ControlMCaucasianControl36
FA0000011TALSCTRL15.12ControlFCaucasianControl49


Pipeline

Rutgers IDTarget ALS IDDescriptionGenderRace/ EthnicityALS or ControlAge at BiopsyAge at OnsetAge at DiagnosisAge at DeathDiagnosisSite of OnsetFamily HistoryAvailability
FA0000021TALSSOD1A4V-
39.7
SOD1A4VALSFCaucasianALS44434345Lab-
supported
probable
RLEALS (Mother)19-Feb-16
FA0000019TALS9-12.3C9orf72 ALSMCaucasianFTD, ALS6040
(FTD),
59 (ALS)
59 (FTD,
ALS)
60Probable ALSLUEALS + FTD (mother; confirmed by autopsy)4-Mar-16
FA0000023TALS9-8.6C9orf72 ALSMCaucasian/
Ashkenazi
Control; brother of C900962paternal aunts w/ ALS; father w/ dementia; sister w/ ALS4-Mar-16
FA0000014TALSTDP-47.10TDP43ALSMCaucasianALS43434344Definite ALSBLE, BUEALS (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 (sheldon@biology.rutgers.edu), director of our distribution facility if you have any issues ordering stem cell lines.

Next steps

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
  • Tools
    • 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 (manish.raisinghani@targetals.org) 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