Department of Defense ALSRP Therapeutic Development Grant

• Secondary validation of lead compounds obtained from screening or by other means to demonstrate target selectivity and mechanism of action,

• Optimization of potency and pharmacological properties, development of structure- activity maps via synthesis, and testing of derivatives and sister compounds,

• Studies on formulation and stability,

• Development of Good Manufacturing Practice (GMP) production methods, and

• Collection of data for FDA IND applications, to include compound characterization, absorption, distribution, metabolism, and excretion (ADME) studies, and dose/response and toxicology studies.

In parallel with lead compound validation and development, applicants are strongly encouraged to assess in vivo efficacy or target engagement (measurement of target binding or proximal downstream effects) in a relevant preclinical ALS model(s).

Applications must include preliminary data and other supporting information relevant to the phase(s) of the preclinical development, such as the following:

• Background data supporting the putative mechanism of action as a viable therapeutic
approach

• An identified bioactive compound or limited group of identified lead molecules with:

• Proof of identity and purity

• Selectivity for the intended target over closely related targets (when the target is known)

• Availability of primary and secondary in vitro bioactivity assays for optimization or structure-activity relationship studies

• Availability of appropriate preclinical animal models of ALS to assess in vivo efficacy or desirable mechanism-specific drug activity at the intended target (target engagement)

Investigators interested in basic research focused on ALS drug discovery are encouraged to apply for the FY17 ALSRP Therapeutic Idea Award (Funding Opportunity Number: W81XWH- 17-ALSRP-TIA), which does not require preliminary data (http://cdmrp.army.mil/funding/alsrp).