Scientists from the University of California, Berkeley report on a chemical ‘photoswitch’ named DENAQ that may be a potential drug for treating patients suffering from blinding diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).
RP and AMD are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. In the paper published in Neuron, the authors led by Dr Richard H Kramer report about a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight, compared to earlier attempts at photoswitch that required very bright ultraviolet light, making it unsuitable for use in patients. In experiments conducted on three-month to six-month-old healthy mice, and on mice carrying a mutation causing nearly all their rods and cones to degenerate by the time they were a month old, a single intraocular injection of DENAQ has been able to photosensitize the blind retina for about 3 days, restoring electrophysiological and behavioral responses with no toxicity. DENAQ also is able to rapidly turns itself off, allowing rapid repeated stimulation of the retina. The researchers compared the retinae of DENAQ-injected mice to untreated healthy mice and found no signs of toxicity for up to 30 days after the injection.
Retinas with damaged rods and cones are subject to several morphological and biochemical changes, making them different from a healthy retina in more than one way. Experiments on mouse strains with functional, nonfunctional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated or dead photoreceptors. Apparently, the degenerated outer retinal cells help in DENAQ photosensitization due to changes in electrophysiological characteristics, while the presence of intact photoreceptors possibly prevent this action. This appears to give it significant advantage, since this selective action on diseased tissue alone may potentially reduce side effects on healthy retina.
DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing. The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD.
The researchers plan on conducting more experiments, including in larger animals before its safety can be established and any clinical trials can be considered.
To watch a video of Dr Kramer explaining his work, click here.
Sources: Neuron, Univ of California, Berkeley, Kramer Lab, The Scientist
Editor's note: The drug appears to have an exciting potential to help patients with retinitis pigmentosa and age-related macular degeneration. There are two thoughts though.
1. Such a drug may only work in advanced stages of the disease, considering we will have to wait for the retinal cells to die before it can act.
2. We also need to know how long the effect of one injection lasts. Such treatment may require repeat injections over a long-term, something similar to Lucentis or Avastin.
RP and AMD are blinding diseases caused by the degeneration of rods and cones, leaving the remainder of the visual system unable to respond to light. In the paper published in Neuron, the authors led by Dr Richard H Kramer report about a chemical photoswitch named DENAQ that restores retinal responses to white light of intensity similar to ordinary daylight, compared to earlier attempts at photoswitch that required very bright ultraviolet light, making it unsuitable for use in patients. In experiments conducted on three-month to six-month-old healthy mice, and on mice carrying a mutation causing nearly all their rods and cones to degenerate by the time they were a month old, a single intraocular injection of DENAQ has been able to photosensitize the blind retina for about 3 days, restoring electrophysiological and behavioral responses with no toxicity. DENAQ also is able to rapidly turns itself off, allowing rapid repeated stimulation of the retina. The researchers compared the retinae of DENAQ-injected mice to untreated healthy mice and found no signs of toxicity for up to 30 days after the injection.
Retinas with damaged rods and cones are subject to several morphological and biochemical changes, making them different from a healthy retina in more than one way. Experiments on mouse strains with functional, nonfunctional, or degenerated rods and cones show that DENAQ is effective only in retinas with degenerated or dead photoreceptors. Apparently, the degenerated outer retinal cells help in DENAQ photosensitization due to changes in electrophysiological characteristics, while the presence of intact photoreceptors possibly prevent this action. This appears to give it significant advantage, since this selective action on diseased tissue alone may potentially reduce side effects on healthy retina.
DENAQ confers light sensitivity on a hyperpolarization-activated inward current that is enhanced in degenerated retina, enabling optical control of retinal ganglion cell firing. The acceptable light sensitivity, favorable spectral sensitivity, and selective targeting to diseased tissue make DENAQ a prime drug candidate for vision restoration in patients with end-stage RP and AMD.
The researchers plan on conducting more experiments, including in larger animals before its safety can be established and any clinical trials can be considered.
To watch a video of Dr Kramer explaining his work, click here.
Sources: Neuron, Univ of California, Berkeley, Kramer Lab, The Scientist
Editor's note: The drug appears to have an exciting potential to help patients with retinitis pigmentosa and age-related macular degeneration. There are two thoughts though.
1. Such a drug may only work in advanced stages of the disease, considering we will have to wait for the retinal cells to die before it can act.
2. We also need to know how long the effect of one injection lasts. Such treatment may require repeat injections over a long-term, something similar to Lucentis or Avastin.
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