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Effective therapies are needed for amyotrophic lateral sclerosis (ALS), a debilitating and fatal motor neuron disease. Cell and animal models of ALS are beginning to reveal possible principles governing the biology of motor neuron-selective vulnerability that implicate mitochondria and the mitochondrial permeability pore (mPTP). Proteins associated with the mPTP are known to be enriched in motor neurons and the genetic deletion of a major regulator of the mPTP has robust effects in ALS transgenic mice, delaying disease onset and extending survival. Thus, the mPTP is a rational, mechanism-based target for the development of drugs designed to treat ALS. Trophos SA has discovered olesoxime (TRO-19622), a small-molecule with a cholesterol-like structure, which has remarkable neuroprotective properties for motor neurons in cell culture and in rodents. Olesoxime appears to act on mitochondria, possibly at the mPTP. Phase I clinical trials of olesoxime have been completed successfully. Olesoxime is well tolerated and achieves levels predicted to be clinically effective when administered orally. It has been granted orphan drug status for the treatment of ALS in the US and for the treatment of spinal muscular atrophy in the EU. Phase II/III clinical trials are in progress in Europe.

The 32nd National Medicinal Chemistry Symposium, held in Minneapolis, MN, USA, included topics covering new developments in the field of medicinal chemistry. This conference report highlights selected presentations on NR2B subtype-selective NMDA receptor antagonists from Merck; selective neuronal nitric oxide synthase inhibitors from Northwestern University; novel GPR119 agonists, suchas GSK-1292263A (GlaxoSmithKline plc), PSN-821 ((OSI) Prosidion) and MBX-2982 (Metabolex Inc); a small-molecule Bcl inhibitor,navitoclax (Abbott Laboratories); and p53-targeting agents from sanofi-aventis and Ascenta Therapeutics Inc, including AT-219.

The clinical success of mAbs continues to reinforce antibody engineering as an essential tool for the development of biologics. Research focused on discovering the next generation of therapeutics has prompted a revisiting of the concept of bispecific antibodies (bsAbs). Recently, clinical programs investigating combinations of mAb therapies have renewed interest in the applications of bsAbs. However, because of challenges with production, efforts directed toward the development of bsAbs have yet to yield a product approved by the FDA. The current status of these proteins implies that the strategies for constructing therapeutic bsAbs will likely require a highly refined design plan at the outset of the engineering process. Antibody fragments are attractive building blocks for the assembly of bsAbs. Of the recombinant antibody fragments, single-chain variable fragments (scFvs) offer the advantage of expression as a single polypeptide, thereby greatly simplifying production. However, issues with stability have plagued these proteins and limit the application of scFvs as therapeutics. Recent advances in selection processes using display platforms have been reported that facilitate the 'evolution' of scFvs to obtain stabilities comparable with those of mAbs. The timely advances in scFv engineering parallel the resurgence of bsAbs and enable the construction of dual-targeting proteins that can be manufactured as therapeutics.

The Bangalore India Bio 2010 conference, held in Bangalore, India, included topics covering new developments in the biopharma industry. This conference report highlights selected presentations on novel therapeutics for the treatment of cancer, including identification of novel benzimidazole, N-subsituted isatin and azetidine derivatives, and an Wnt antagonist. In addition, presentations from several biopharma companies and universities are highlighted, including Proteomics International Pty Ltd, Oxford BioMedica plc, AnaptysBio Inc, SIOGEN Biotech, RV College of Engineering and Indian Institute of Science.

The Purines 2010: Adenine Nucleosides and Nucleotides in Biomedicine meeting, held in Tarragona, Spain, included topics covering new findings in the field of purinergic signaling and the development of purine-based drugs. This conference report highlights selected presentations on developments in purinerigic signaling, medicinal chemistry, the therapeutic potential of purine-based drugs, and the role of purines and adenosine receptors in neurodegenerative disorders, sickle cell disease, bone homeostasis, pulmonary fibrosis and pain. Investigational drugs discussed include CF-101 (Can-Fite BioPharma Ltd/NIH/Kwang Dong Pharmaceutical Co Ltd/Seikagaku Corp) and denufosol tetrasodium (Cystic Fibrosis Foundation Therapeutics Inc/Inspire Pharmaceuticals Inc).

The 16th Annual Conference of the European Generic Medicines Association (EGA), held in Rome, included topics covering new developments and challenges in the generic medicines industry in Europe. This conference report highlights selected presentations on developments for generics in the Italian healthcare system, a summary of the EGA pharmaceutical sector inquiry on the delayed market entry of generics, developments and trends in the European generics market, the evolution and growth of the global generics industry, and a CEO perspective on the challenges facing the industry.

CH-1504, being developed by Chelsea Therapeutics Inc under license from the University of South Alabama, is an orally available, metabolically inert antifolate, for the potential treatment of rheumatoid arthritis (RA). CH-1504 is an analog of methotrexate (MTX) but differs from the classical antifolates because of an improved safety and tolerability profile. A significant proportion of the toxicity profile of MTX can be attributed to its polyglutamylated and hydroxylated metabolites; therefore, metabolism-blocked antifolates, such as CH-1504, have been designed to prevent the accumulation of toxic metabolites. Preclinical studies and phase II clinical trials indicated that CH-1504 and MTX inhibit dihydrofolate reductase activity with equal potency. In a phase II, proof-of-concept trial in patients with RA, CH-1504 was associated with improved tolerability and reduced hepatotoxicity as compared with MTX; in addition, improvements in the American College of Rheumatology response rates were similar following treatment with either CH-1504 or MTX. Furthermore, Chelsea Therapeutics are developing the L-isomer of CH-1504, CH-4051, which displays improved in vitro potency over with racemate and appears to be Chelsea Therapeutics' preferred candidate for future development. Inert antifolates appear to be a promising drug class for the treatment of RA because the disease-modifying properties of MTX are retained, but the therapeutic window of the inert antifolates is improved. However, further trials are required to establish the efficacy and long-term safety in a wider population of patients with RA.

Informa Life Sciences' Fifth Annual Conference on Cell-Based Assays, held in Cologne, Germany, included topics covering new technical developments in the field of cell-based assays. This conference report highlights selected presentations on label-free cell-based assays and the application of high-content analysis to drug discovery.

The 14th International Congress of Parkinson's Disease and Movement Disorders, held in Buenos Aires, included topics covering new therapeutic developments in the field of Parkinson's disease and other movement disorders. This conference report highlights selected presentations on drug treatments for movement disorders, including safinamide (Merck Serono SA), PYM-50028 (Phytopharm plc), droxidopa, pardoprunox (Abbott Laboratories); treatment considerations for dystonia; exploiting existing drugs for new indications; and using genetics to assess drug therapy responses.

The 32nd National Medicinal Chemistry Symposium, held in Minneapolis, MN, USA, included topics covering new developments in the field of medicinal chemistry. This conference report highlights selected presentations on Hsp90 inhibitors and Hsp70 inducers, such as KU-32 and KU-174 (University of Kansas); natural products in drug design, such as minnelide (University of Minnesota) and tylocrebrine; novel compounds from Merck for metabolic and cardiovascular diseases, such as MK-7725, a series of DDP4 inhibitors and KV1.5 ion channel antagonists; and the discovery of the VEGFR2 kinase inhibitor AMG-429 (Amgen Inc).