Abstract: The invention provides a clinically useful protocol for delivery of recombinant nervous system growth factors into the aging mammalian brain. The invention is particularly useful in tempering and reversing the loss of neurological function in the aging mammalian brain, by (a) correlating loss of cortical fiber density to impairment of neurological function in the normal, aging brain; and (b) providing minimally invasive means by which such losses may be reversed. To these ends, a method is provided by which a growth factor-encoding transgene is delivered to, and expressed in, preselected sites within the brain, to stimulate growth of neurons at, and at a distance from, each delivery site.

Abstract: Mutant “pro-neurotrophins” whose corresponding growth factor is secreted more efficiently from host cells than wild-type growth factor. Such improved activity is obtained through substitution of a residue in the precursor protein (“prepro”) region of a pro-form of a growth factor. Pro-neurotrophins contain at least one conserved asparagine-based N-glycosylation site present upstream of the cleavage site for separation of the corresponding neurotrophin. The invention substitutes the asparagine with a basic residue, such as serine. At the higher levels of extracellular growth factor achieved by the invention, the bioavailability, and therefore the therapeutic potential of the corresponding mature protein is enhanced.

Abstract: The invention provides a clinically useful protocol for delivery of recombinant nervous system growth factors into the aging mammalian brain. The invention is particularly useful in tempering and reversing the loss of neurological function in the aging mammalian brain, by (a) correlating loss of cortical fiber density to impairment of neurological function in the normal, aging brain; and (b) providing minimally invasive means by which such losses may be reversed. To these ends, a method is provided by which a growth factor-encoding transgene is delivered to, and expressed in, preselected sites within the brain, to stimulate growth of neurons at, and at a distance from, each delivery site.