Technologies

Pharmaceuticals & Vitamin D : Musculoskeletal

Pharmaceuticals & Vitamin D Portfolios

Technologies

Hormone Analogs for Treating Hypoparathyroidism

UW–Madison researchers have developed backbone-modified peptide analogs of PTH (1-34) that could be used to treat hypoparathyroidism, a condition caused by decreased gland function resulting in low blood calcium levels, abnormal muscle activity and other symptoms. The analogs were generated by replacing certain α-amino acid resides with β-amino acid residues.

The analogs were used to assess the impact of backbone modifications on receptor state-selectivity. The results show that diverse binding profiles can be achieved via this strategy and give rise to distinct behaviors in vivo.
P130312US03

Vitamin D Analogs “WT-51” and “WT-52” Boost Bone and Skin Health

UW–Madison researchers have developed two new vitamin D3 analogs, (22E)-(24R/S)-2-methylene-22-dehydro-1α,24,25-trihydroxy-19-nor-vitamin D3, known as WT-51 and WT-52. These compounds show activity similar to that of the native hormone in stimulating intestinal calcium transport, but are up to 10 times more potent in promoting cell differentiation and gene transcription.
P130007US02

Treating X-Linked Hypophosphatemia (XLH), Bone Deformity and Other Renal Phosphate Wasting Disorders

UW–Madison researchers have developed methods to treat XLH, and potentially other renal phosphate wasting disorders, using polyarginine peptides. The peptides stimulate the 7B2-SPC2 protein complex, overcoming a primary abnormality resulting from the PHEX gene mutation responsible for the cascade of abnormal protein functions that lead to the XLH phenotype.

Administered alone or with other pharmaceutical agents, the arginine peptides work by enhancing FGF-23 degradation into inactive fragments and suppressing FGF-23 production. The resultant normalized levels of FGF-23 and other proteins completely rescue the HYP phenotype, including the abnormalities in the serum phosphate and bone mineralization.
P100323US02

Novel Subtype of Botulinum Toxin for Prolonged Effectiveness

UW–Madison researchers have discovered and purified a novel subtype of botulinum neurotoxin, BoNT/A5. The new subtype was found in a strain of the bacteria (A661222) maintained in the researchers’ lab collection. The A5 sequence is very similar to A1; most of the differences are in areas known to interact with neutralizing antibodies. This means it may be effective even when patients have developed resistance to BOTOX and other treatments.
P09050US02

Tat-Utrophin as a Protein Therapy for Muscular Dystrophies

UW-Madison researchers have developed a fusion protein between utrophin and the TAT sequence from HIV, which is used to transport molecules into cells, for the treatment of muscular dystrophies, including DMD. This protein-based therapeutic provides the first effective treatment for these currently fatal conditions.

The TAT sequence provides a cell signal that leads to the internalization of utrophin in muscle cells. Once in the muscle cells, the utrophin is able to compensate for the lack of dystrophin, reducing or eliminating the disabling effects of dystrophinopathic conditions.

The inventors successfully treated a mouse model for DMD by injecting the fusion protein intraperitoneally. The TAT-utrophin localized to the target area of muscle, resulting in significant improvement in several key disease parameters.
P06414US

Use of Neuropeptides for Ligament Healing

UW-Madison researchers have developed a method of using neuropeptides to shorten the healing period and increase the strength of ligaments damaged by traumatic injury, disease or disuse. The researchers demonstrated that several neuropeptides play a role in ligament healing. To treat ligament damage, one or more of these neuropeptides, which include calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), dynorphin, enkephalin, galanin, neuropeptide Y (NPY), neurotensin, somatostatin, substance P (SP), thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP), are delivered directly to the damaged ligament. Experiments in rats showed that damaged medial cruciate ligaments (MCLs) treated with the neuropeptides were as strong as or stronger than uninjured MCLs.
P04056US

Method to Diagnose and Treat Degenerative Joint Disease

UW-Madison researchers have developed methods for detecting and treating joint disease, particularly in joints containing a functionally important intra-articular ligament or tendon. To diagnose joint or ligament degeneration, a sample is taken from a joint or ligament and tested for the expression of cathepsin K, cathepsin S, or tartrate-resistant acid phosphatase (TRAP). Because these enzymes are up-regulated during the development of inflammatory arthritis or ligament degeneration, increased levels indicate the presence of disease. Treatment of joint or ligament disease would involve inhibiting the activity of cathepsin K, cathepsin S, or TRAP.
P03092US