Zinc/AMD, SUN Pharma/Pipeline, Retina Implant

German Eye Implant Delivers Basic Images to Blind

Initial results from a pilot study show that a chip developed by German scientists is capable of partially restoring basic sight to the blind. Blind subjects were able to see beams of light after scientists implanted an electric microchip in their retina, showing that the chips fundamentally work, according to Eberhart Zrenner, head of Tübingen University's Ophthalmology Research Institute.

Similar to the photoreceptor cells they are intended to replace, the chips collect light information and pass it in the form of electrical impulses along existing optic nerves to the brain, where the information is processed, Zrenner said. Still in the research stage, the therapy is only suitable for people who were once able to see but whose eyes suffer from damaged photoreceptors. The implant is not able to restorve vision to patients with a damaged optical cortex or who were born blind.

Chips intended for basic orientation

The implant is not able to help in all cases of blindness The people who were treated with the implant could recognize light in certain forms and patterns, locate light sources like lights and windows. Some of the patients were also able to locate bright objects, such as cups and plates, on a dark background. Zrenner said the project's next stage involves implanting chips in six other patients' maculas, where photoreceptors are especially dense, to see if better results can be achieved. "The chips did not lay on the spot where vision is the sharpest, but on the periphery, which could have led to their signals from the retina not being optimally processed by the brain," he said.

The project's goal is to develop an implant that would give patients enough sight to orient themselves in new rooms and spaces and recognize large objects. The pilot study intends to determine the implant's safety and the human body's tolerance to accept objects placed inside the eye on the basis of a four-week temporary implantation.


Chips to be ready by 2009

The first chips are expected to be ready for market by 2009, according to Walter Wrobel, head of the Reutlinger Retina Implant, a company that developed out of the research project and created the implant, which is about the size of a grain of rice. It costs 25,000 euros ($33,000). Though they are not expected to be restore perfect vision to the blind, the implants do represent a major technological advance, said Karl Ulrich Bartz-Schmidt, a retinal surgon in Tübingen. "Aviation pioneers did not fly over the Atlantic right away," he said. "You should not expect too much from the technology. It would be a great success if we could eventually give patients back a limited ability to orient themselves."

Several German researchers are also working on similar implant projects for over 10 years, according to Christian Ohrloff, the head of the German Ophthalmology Society.


High Zinc Levels in Eyes Linked to AMD

A U.K. study finds that elevated levels of zinc in the eyes may play a role in the development of age-related macular degeneration (AMD), the leading cause of blindness among elderly people in the developed world, BBC News reported. The study, led by London's Institute of Ophthalmology, found that the eyes of people with AMD have high levels of zinc in drusen, microscopic structures in the eye that are an early sign of AMD.

"Zinc had previously been shown to contribute to the formation of plaques in the brains of patients with Alzheimer's disease, so it was logical for us to test the idea that zinc might also contribute to the formation of plaque-like drusen in the eye as well," said researcher Dr. Imre Lengyel. "AMD can be considered as the Alzheimer's disease of the eye, in that both involve the build-up of proteins and metals like zinc and copper into microscopic clumps," Lengyel said.



Sun Pharma discloses NCE & NDDS pipeline

In a detailed presentation yesterday, management shared details of its NCE and NDDS programs that the team of scientists at its research center, SPARC, have been working on. 4 NCEs and products based on 4 NDDS platform technologies were discussed.Sun Pharma shared information on its therapeutic analogue based programs in the allergy/ inflammation area. Modification of poorly absorbed molecules is another focus area.

SUN 1334 H, a selective histamine receptor antagonist, is currently in Phase II clinical trials in the US. This is an antiallergic used for seasonal and allergic rhinitis, urticaria, etc. In preclinical studies, Sun 1334H was found to have high specificity for H1 receptors, and this indicates a low side effect profile. Sun 1334H was found to have a clean profile with fast onset of action, was non sedating and offered efficacy similar to cetirizine. Phase I trials in Europe indicated that the molecule was well tolerated, effective and appropriate for once-a-day dosing. Phase III for this lead is estimated to begin in 2008.

SUN 461, an anti-inflammatory for asthma and COPD, is being developed as an inhalation drug. This soft corticosteroid is a glucocorticoid receptor agonist, with similar activity but significantly lower side effects whe compared to other marketed steroids.

SUN 44, a prodrug of gabapentin for the treatment of neuropathy and seizures, uses molecular modifications in the structure for better absorption. In preliminary animal studies, this molecule was found to be far better absorbed and safer than existing products. Its profile indicates higher blood availability, a once-a-day formulation and higher safety.

SUN 09 is a prodrug of a currently marketed drug used as a skeletal muscle relexant for spasm related disorders. This molecule’s physicochemical and structural features have been modified for better absorption, and it seems to be easy to formulate as an injectable and once-a-day dosage form. Preclinical and acute toxicity studies on this molecule are ongoing.

SUN 44, 09 and 461 are at preclinical stages. IND filing and Phase I for these projects will begin in 2008.

Delivery system based projects: Four delivery system based platforms and the projects based on these were highlighted.

Dry Power Inhaler (DPI): The novel DPI for asthma and COPD delivers a uniform dose over a range of patient effort and can be used both with existing steroid and bronchodilator combinations, as well as NCE steroid molecules. It can also be modified for systemic delivery of drugs to lungs. This easy to operate inhaler– just 3 steps of open, inhale and close - will comply with US FDA and European regulatory requirements. Our DPI is designed to deliver uniform dose irrespective of patient inhalation effort, eliminate double dosing or dose wastages and ease use by children, adults as well as elderly thus addressing shortcomings of other devices. A product based on this novel DPI is likely to be launched in semi-regulated markets by 2009, and an NDA will be filed for regulated markets by 2011.

Controlled-release drug delivery systems

The Gastro Retentive Innovative Device (GRID) is designed to retain and release a drug over an eight hour span, ideal for an once- a - day system. The release profile can be tailored to give a combination of instant and sustained release profiles.

Baclofen GRS, a once-a-day formulation as compared to twice or thrice daily administration of the competing product, is being developed to treat muscle spasticity. For India, clinical trials have been completed successfully after which the product was approved. For the US, IND filing is likely in 2007.

Wrap matrix: This multi-layered matrix based tablet is designed to offer a controlled release of high dose and high solubility products. This design has an advantage over competing technologies, where it is difficult to reproduce bioavailability. Metoprolol XL with a once-a-day advantage, has been launched in India. A few ANDAs using this technology have been filed with the USFDA.

Tobramycin + Dexa ophthalmic solution: Unlike the competing product which is a suspension causing gritty feeling in the eye, our product is being developed as a clear solution for use in the prophylaxis of infections after cataract surgery. A pre-IND meeting with the FDA has been completed, with likely IND filing for 2007.

Depot Technology that uses long-acting injectable microparticles for slow/sustained drug release over a month to several months using biocompatible and biodegradable polymers. Our product uses a conventional needle, unlike the competing product where tiny rods are implanted, thus reducing patient trauma and pain. A GnRH analogue is in preclinial trials, with clinical studies slated for 2008. A somatostatin analogue is in clinical studies in India.

Nanoemulsion based products that offer higher drug localization to the cancer cells and fewer side effects were discussed. Our product uses an unique encapsulation process to achieve more than 98% encapsulation of bioactive substance, unlike competing products. Two cytotoxic products are being developed with this technology.