FWD: TDR WorkPlan96: I-CHEM
Patricia de Oliveira
patricia at bdt.org.br
Thu Mar 21 10:32:28 BRT 1996
--- Forwarded mail from hatak at who.ch
Date: Tue, 19 Mar 96 17:57:31 CET
From: hatak at who.ch
To: TDR-Scientists at who.ch
Subject: TDR WorkPlan96: I-CHEM
Resent-From: Listas Ecologia Biologia <ecobio at Venezuela.MIT.EDU>
UNDP/World Bank/WHO
Special Programme for Research and Training in Tropical Diseases
(TDR)
WORKPLAN
of the
STEERING COMMITTEE ON DRUGS FOR
AFRICAN TRYPANOSOMIASIS, CHAGAS DISEASE
AND LEISHMANIASIS
(I-CHEM)
Rationale
Only a handful of drugs are available for the treatment of each of the
three diseases. Some of them were developed over half a century ago.
Besides, they are plagued by various limitations, such as acute
toxicities, low efficacies and emergence of parasite resistance. New
therapies are urgently needed in all three areas. The kinetoplastidae,
the group to which the three parasites belong, have many intriguing
biological features which are similar and could be attractive targets
for chemotherapy. In 1991, TDR decided to group together all activities
related to the search and development of new drugs for the three
diseases under one Steering Committee (I-CHEM) to maximize efforts and
optimize resources. Thus, any approach to the discovery of drugs for
one disease should be evaluated for relevance to the other two diseases.
Objectives
The objectives of the programme are to discover and identify new
chemical leads against the three diseases, to exploit and optimize these
leads to the stage of identifying specific molecules with clinical
therapeutic potential and to take such molecules through the various
stages of development and clinical trials necessary to establish them as
viable drugs.
Specific objectives
To identify areas which in the short to medium term are most promising
and would lead to the development of new drugs. The inhibition of
sterol biosynthesis, polyamine/S-adenosylmethionine/trypanothione
biosynthesis and/or function, and possibly protease inhibition were
considered as priority.
Expected Outcomes
Identification of lead compounds which would be taken through
preclinical and clinical studies to registration for the treatment of
any of the three diseases.
How to apply
Drug discovery should be the primary objective of any research proposal
submitted to I-CHEM. Proposals should be concerned with specific types
of inhibitors, where activity in the series has been demonstrated -
preferably in vivo - or in specific systems or metabolic pathways. It
should be shown that inhibition will have lethal consequences for the
parasite. Due to present financial constraints, long-term projects
concerning enzymes or pathways which might ultimately have possible
therapeutic significance will not be supported during the biennium
(1996/97). Moreover proposals, which are not concerned, wholly or in
part with chemical synthesis of potential inhibitors, should indicate
clearly where compounds for study will be obtained and what forms of
collaboration for such provision will be established.
I-CHEM is currently supporting three screening centres where compounds
can be screened and evaluated against parasites of all three diseases
using both in vitro and in vivo models. It is expected that Principal
Investigators receiving support from I-CHEM will make use of these
facilities and submit compounds for evaluation where appropriate.
I-CHEM will collaborate with industry in combinatorial library screening
of compounds and with scientists in the supply of combinatorial targets
for these activities.
The next meeting of the Steering Committee on Drugs for African
Trypanosomiasis, Chagas Disease and Leishmaniasis, (I-CHEM) will take
place from 21-24 October 1996. Proposals for 1996 should be submitted
by 20 August 1996.
All correspondence on Drugs for African Trypanosomiasis, Chagas Disease
and Leishmaniasis (I-CHEM) should be sent to:
F.A.S. KUZOE, Manager
Steering Committee on Drugs for African Trypanosomiasis,
Chagas Disease and Leishmaniasis, (I-CHEM)
Special Programme for Research and Training in Tropical Diseases
World Health Organization
CH-1211 Geneva 27
Switzerland
Telephone: (41.22) 791.3867
FAX: (41.22) 791.4854
Email: rosenstockm at who.ch
--------------- WorkPlan in List format follows -----------------------
Steering Committee on Drugs for African Trypanosomiasis,
Chagas Disease and Leishmaniasis (I-CHEM)
Workplan - 1996/97
OBJECTIVES
PLANNED ACTIVITIES
---STATUS
A. Identify new chemical entities against the three diseases
A.1 Update targets for the three parasites - support
priority research areas identified during
1994-95 biennium, polyamines, sterols
---In Progress
A.2 Identify potential compounds, biologicals and
research areas which could lead to new drugs against
the three diseases through collaborative research
networks and TDR-supported screening centres.
---In Progress
A.3 Acquire chemical compounds from industry and through
commissioned research etc. for submission to
TDR-supported screening centres. (TDR
responsibility)
---In Progress
A.4 Identify a supply of recombinant targets for
combinatorial screen (e.g. SAMDC, ODC, Glycolytic
enzymes, AGCPR, DHFR)
---In Progress
B. Develop new therapeutics against the three diseases
B.1 Conclude phase I/II clinical trials for the drug
aminosidine against visceral and mucosal
leishmaniasis in Peru and India and acquire
necessary data for registration.
---IVQ95 - IVQ96
(4th quarter 95 - 4th quarter 96)
B.2 Identification of oral agent and initiation of
trials
---IQ96 - IQ97
B.3 Further initiation of trials of oral or topical
agents
---IQ96 - IQ98
B.4 Pursue clinical studies with CG 40215 for
trypanosomiasis
---IVQ95 - IVQ96
B.5 Expedite research including all pre-clinical studies
such as toxicology, stability studies, presentation,
efficacy in animals and documentation for
registration on one candidate compound to meet
requirements for clinical trials.
---IVQ96 - IVQ98
B.6 Encourage innovative research on chemotherapy of
PKDL
---IVQ96
(i-chem.txt)vbb19mar96
--- End of forwarded message from hatak at who.ch
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