Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Pharmacyclics (PCYC) -- Ignore unavailable to you. Want to Upgrade?

To: squetch who wrote (494)	8/26/1999 11:00:00 AM
From: Biomaven	Read Replies (3) \| Respond to of 717

People have probably seen this stuff at the pcyc web site: pcyc.com But for those that haven't, here's what they say about Antrin: PHOTOANGIOPLASTY OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE The interaction of light with biological systems is a well known phenomenon exemplified by photosynthesis, the process by which plants capture light energy through the use of chlorophyll. By the early 20th century it had been shown that certain chemical agents could be activated by light to mediate particular biological processes including the destruction of diseased tissues. During the period between 1924 to 1948 it was discovered that porphyrins, compounds similar to chlorophyll, could selectively localize in certain organs and tissues including the liver, cancerous tumors, and tissues containing high levels of cholesterol and lipoproteins. Over the past decade there has been increasing interest in developing both naturally occurring and synthetic porphyrins that are activated by light and can be used as therapeutic agents (otherwise known as photosensitizers) for a variety of diseases. In the photoangioplasty procedure, a photosensitizer that accumulates in the diseased plaque is administered to the patient, and then the diseased site is illuminated with an appropriate frequency and energy dose of far red light, delivered by an intravascular catheter containing an optical fiber, that is absorbed by the drug. The photosensitizer is activated to a short-lived excited state that may convert to a long-lived triplet state. This triplet state of the molecule interacts with oxygen to create singlet oxygen, which causes irreversible damage to cellular components. The photosensitizer does not react directly with the cellular targets and is capable of repeated generation of singlet oxygen. This treatment approach may eliminate atherosclerotic plaque without damage to the normal blood vessel wall, thereby potentially eliminating the need for anticoagulants and reducing the frequency of restenosis. Most of the damage induced by photoangioplasty is accomplished by singlet oxygen. The molecule is highly reactive, limiting its diffusion capabilities (singlet oxygen has an estimated diffusion distance in cells of less than 0.1 micrometers.) Therefore, it is essential that the photosensitizer be at the target site when activated by the light. Acute effects mediated by singlet oxygen include severe damage to various cell membranes including plasma, mitochondrial, lysosomal, endoplasmic reticulum, and nuclear membranes; inhibition of enzymes, including mitochondrial, DNA repair, cytosolic, and lysosomal enzymes; and inactivation of membrane transport systems. Ultimately, the diseased tissue in which the photosensitizer has localized should be destroyed with little or no damage to the surrounding normal tissue. Ideally, a photosensitizer for photoangioplasty should accumulate selectively in atherosclerotic plaque and be readily activated by light capable of penetrating through blood to reach the drug. Other important features include safety, lack of skin phototoxicity, and simple administration of the agent to the patient. To date, there are no photosensitizers approved by the U.S. Food and Drug Administration (FDA) for treatment of atherosclerosis. ATHEROSCLEROTIC CARDIOVASCULAR DISEASE Atherosclerosis is a progressive and degenerative vascular disease in which cholesterol and other fatty materials are deposited in the walls of blood vessels, forming a build-up known as plaque. The accumulation of plaque narrows the interior lumen of the blood vessels, thereby reducing blood flow. Atherosclerosis in the coronary arteries can lead to heart attack and death. In peripheral vessels, atherosclerosis can lead to decreased mobility, loss of function, and other complications such as strokes. Current treatments for atherosclerosis include surgery and other techniques aimed at removing or relieving the plaque. Procedures utilizing intravascular devices to mechanically compress or remove the obstructing lesion include balloon angioplasty and atherectomy. These procedures require the use of anticoagulant drugs and, frequently, the use of stents to reduce the incidence of restenosis, which results from traumatic damage to the vessel wall. Generally, these techniques have been limited to treating only localized sections of the diseased vessel. The optimal interventional treatment for atherosclerosis should effectively eliminate atherosclerotic plaque without the need for anticoagulant drugs or stent placement to prevent restenosis. Because atherosclerosis is a diffuse disease, therapies which can be used over long segments of the affected vessel offer significant advantages over treatments limited to localized sections of the vessel. Pharmacyclics' Patent Position Pharmacyclics is the exclusive licensee of several patents and applications, both U.S. and internationl, directed to photoangioplasty, including treatment of atherosclerotic cardiovascular disease and the production of singlet oxygen. These include U.S. composition of matter patents to the basic texaphyrins and method patents to photoangioplasty of atherosclerosis and to the production of singlet oxygen, as well as pending applications to further methods and compositions.